The role of tumor necrosis factor in the regulation of antigen presentation by human monocytes.
Human peripheral blood monocytes pretreated with human recombinant tumour necrosis factor alpha (rTNF) showed an enhanced ability to present a soluble antigen, a purified protein derivate of tuberculin, to autologous T lymphocytes as assessed by their increased proliferation in vitro. This enhancing activity was due to TNF and not impurities in TNF preparations as anti-TNF antibodies abolished this phenomenon. The rTNF-treated monocytes showed an increased expression of HLA-DR molecules and enhanced co-stimulatory activity in the murine thymocyte assay. Pretreatment of monocytes before an antigen pulse with anti-TNF mAb inhibited antigen presentation, which indicated that endogenously produced TNF was involved. These studies thus suggest that TNF acts in an autocrine fashion and enhances the ability of monocytes to present protein antigen. It is unclear at present whether this effect is due to the modification in antigen processing, expression of MHC class II molecules, or other factors (IL-1, IL-6, adhesion molecules, etc.) that are important for the induction of T cell response to a nominal antigen. The enhancement of the antigen presenting capacity of monocytes/macrophages may be the additional mechanism of pro-inflammatory activity of TNF.
Zembala
M
M
Department of Clinical Immunology, Copernicus Medical School, Cracow, Poland.
Kowalczyk
D
D
Pryjma
J
J
Ruggiero
I
I
Mytar
B
B
Klysik
J
J
Stec
W J
WJ
D000911:Antibodies, Monoclonal; D000938:Antigen-Presenting Cells / Q000276:immunology*; D000941:Antigens; D006684:HLA-DR Antigens; D006801:Humans; D066298:In Vitro Techniques; D009000:Monocytes / Q000276:immunology*; D014373:Tuberculin / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D000941:Antigens; D006684:HLA-DR Antigens; D014373:Tuberculin; D014409:Tumor Necrosis Factor-alpha